Processing of food begins in the oral cavity where food is mechanically broken down by mastication, lubricated with saliva, and enzymatically processed by amylase present in the saliva. Processing continues in the stomach where food is liquefied by gastric juices and enzymes secreted by the cells lining the stomach to produce chyme. Chyme enters the small intestine via the pyloric sphincter for further processing by bile salts produced by the liver and digestive enzymes produced by the pancreas. The small intestine absorbs most components from chyme through its walls, and the large intestine subsequently processes components that are not absorbed by the small intestine. Finally, the large intestine propels waste products into the colon, where they remain, usually for a day or two, until the feces are expelled by a bowel movement.
Typically, food includes proteins, carbohydrates, and fats. Each of these components passes through specific digestive and metabolic compartments. Proteins are first digested by enzymes in the juice of the stomach. Further digestion of the protein is completed in the small intestine. Here, several enzymes from the pancreatic juice and the lining of the intestine carry out the breakdown of huge protein molecules into amino acids. Amino acids can be absorbed from the hollow of the small intestine into the blood and then be carried to all parts of the body to build the walls and other parts of cells. Carbohydrates are broken into simpler molecules by enzymes in the saliva, in juice produced by the pancreas, and in the lining of the small intestine. For example, starch is digested in two steps. First, an enzyme in the saliva and pancreatic juice breaks the starch into molecules called maltose. Then, an enzyme in the lining of the small intestine (maltase) splits the maltose into glucose molecules that can be absorbed into the blood. Glucose is carried through the bloodstream to the liver, where it is stored or used to provide energy for the work of the body. Also, table sugar is digested by an enzyme in the lining of the small intestine, which converts it into glucose and fructose, each of which can be absorbed from the intestinal cavity into the blood. Milk contains yet another type of sugar, lactose, which is changed into absorbable molecules by an enzyme called lactase, also found in the intestinal lining.
Fat molecules are first dissolved in watery content of the intestinal cavity. Bile acids produced by the liver act as natural detergents to dissolve fat in water. Enzymes then break the large fat molecules into smaller molecules, some of which are fatty acids and cholesterol. The bile acids combine with the fatty acids and cholesterol and help these molecules to move into the cells of the mucosa. In these cells the small molecules are formed back into large molecules, most of which pass into vessels (called lymphatics) near the intestine. These small vessels carry the reformed fat to the veins of the chest, and the blood carries the fat to storage depots in different parts of the body.
Sometimes, a patient takes an abnormally long time to process and digest food, or a patient processes and digests food too quickly. This abnormal digestive behavior can be contributed to a disorder that affects the digestive system or the metabolic system, whether it is a disorder in the stomach or a disorder beyond the stomach. Commonly, a disorder occurs in the stomach that causes food to be emptied from the stomach into the small intestine too quickly or after too long of a time. Stomach emptying disorders can be diagnosed by measuring the rate at which a meal empties the stomach and enters the small intestine (the “gastric emptying rate”). When the rate is accelerated, undigested food is prematurely dumped from the stomach to the small intestine, giving rise to the condition termed “rapid emptying” or otherwise known as the dumping syndrome. Conversely, when the rate is decelerated, the movement of ingested food from the stomach to the small intestine is delayed, giving rise to the condition termed “delayed emptying” otherwise known as gastroparesis.
Two known tests for measuring gastric emptying rates are gastric scintigraphy tests and breath tests. In scintigraphy testing, a patient ingests a meal including at least one edible food, a component of which has been radiolabeled. The gamma emission from the radiolabel is measured by a scintillation camera as the labeled food is emptied from the stomach. Scintigraphy measurements of gastric emptying are direct, since the camera directly measures the amount of gamma emission from that portion of the radiolabeled meal retained in the stomach. In breath testing, a patient ingests a meal that includes a non-radioactive marker or label such as a stable isotope of carbon, carbon—13, denoted as 13C. As the non-radioactive labeled edible food is processed by the digestive tract and subsequent metabolic processes, a labeled component, such as 13CO2, is produced which can be detected in the patient's breath. In contrast to scintigraphy, measurement of gastric emptying using breath testing is indirect. These two tests for measuring gastric emptying rates are limited to evaluating digestive disorders within only the stomach.
In other cases, a patient suffers from a disorder that occurs beyond the stomach. For example, the disorder can occur in the small intestine. In some cases, a patient might suffer from a shortage of the lactase enzyme in the small intestine, resulting in lactose intolerance. Tests for lactose intolerance include a hydrogen breath test. In this test a loading dose of approximately 2 grams of lactose in water per kilogram of body weight is administered to the patient. A baseline, pre-dose, breath sample is collected. After ingestion, additional breath samples are typically collected out to 3 hours. Hydrogen concentrations in excess of 20 parts per million compared to the baseline sample are considered indicative of lactose non-absorption. The abnormal amount of hydrogen is generated by bacterial fermentation of the lactose farther down the gut (colon) as a result of non-absorption in the small bowel. In other cases, a patient might suffer from a bacterial overgrowth in the small intestine, which can interfere with digestion and absorption of foods. Such a bacterial overgrowth can be detected by administering a 13C-xylose breath test to a patient. This test utilizes the simple 5-carbon carbohydrate xylose in which one or more of the carbon atom positions in the xylose molecule has had naturally occurring 12C atoms replaced (or “labeled”) with 13C atoms. 13C-labeling in substrates like xylose may be achieved at isotopic purity levels exceeding 99%. The principle of this breath test is that the abnormal levels of small bowel flora can be detected by measuring the amount of 13CO2 generated from bacterial 13C-xylose metabolism. Both the hydrogen breath test and the 13C-xylose breath test are limited to detecting disorders in the small intestine. In addition, these tests only measure activity related to the ingestion of a carbohydrate, and not proteins or fats.
In yet other cases, a patient might suffer from a metabolic disorder than occurs in an organ such as the pancreas or the liver. For example, a liver might not be functioning correctly, and liver functions can be assessed using a 13C-methionine breath test, a 13C-glucose breath test, or a 13C aminopyrine breath test. Again, these tests are limited to detecting disorders in the liver. In addition, in each of these tests, the 13C labeling of each respective compound may be achieved at levels exceeding 99% 13C isotopic purity.
Thus, while tests for measuring digestive or metabolic disorders are known, these tests are highly specific and use labels that are synthetically incorporated into a single specific molecule (substrate). For example, the 13C-xylose test uses a 13C label incorporated only into xylose, the 13C-methionine breath test uses a 13C label incorporated only into methionine, the 13C-glucose breath test uses a 13C label incorporated only into glucose, the 13C-aminopyrine breath test uses a 13C label incorporated into aminopyrine, and so on. As a result, these tests have been intended and limited to evaluating digestive or metabolic disorders within a single compartment and through a single metabolic pathway, for example only in the liver. As a result, if one of these tests yields a negative result (indicating that no disorder in the respective compartment is taking place), a clinician cannot assume that all of the patient's digestive and metabolic compartments are operating correctly. Instead, a clinician must perform additional tests at separate settings to evaluate additional compartments. It is also unfeasible to subject a patient to such additional testing, in order to obtain an overall digestive and metabolic assessment. Thus, it would be desirable to provide a simple test method for evaluating all of a patient's digestive and metabolic compartments. In addition, it would be desirable to provide a method for determining whether a digestive disorder occurs within the stomach or beyond the stomach.